the human microbiome and colorectal cancer · quality control standards to evaluate reproducibility...

The human microbiome and colorectal cancer

Emily Vogtmann, PhD, MPH

Research Fellow

Metabolic Epidemiology Branch

Division of Cancer Epidemiology & Genetics

April 20, 2017

2

Outline

Introduction to the human microbiome Technologies to assess the microbiomeHuman microbiome and colorectal cancer Future directions

3

Outline

Introduction to the human microbiome Technologies to assess the microbiomeHuman microbiome and colorectal cancer Future directions

4

Microbiota and the tree of life

Microbes Bacteria Archaea Fungi Protists Viruses

Microbiome: collection of microbial genes

Kutschera (2011) Biol Direct & Pace (1997) Science

5

Alpha and beta diversity

Forest 1 Forest 2

Alpha diversity = 3 Alpha diversity = 6

Alpha diversity• Counts (Taxonomy/OTUs)• Shannon index• Simpson index• Chao1• PD tree

Beta diversity• Bray-Curtis• UniFrac

Beta diversity2 shared5 different

6

PCoA plot: Clustering by body site

The Human Microbiome Project Consortium (2012) Nature

7

Outline

Introduction to the human microbiome Technologies to assess the microbiomeHuman microbiome and colorectal cancer Future directions

8

History of microbial research

Image: http://learn.genetics.utah.edu/content/microbiome/study/

9

Present day study

Images from: http://legacy.owensboro.kctcs.edu/gcaplan/anat2/study%20guides/apii%20study%20guide%20k%20digestive%20anatomy.htm, http://davidql.github.io/scope_talk/emoji_poop.png, http://dnatech.genomecenter.ucdavis.edu/wp-content/uploads/2013/10/Miseq.png, and reproductions from Morgan XC et al. (2012) PLoS Comp Biol

10

Fecal collection methods

No Solution RNAlater 95% Ethanol

11

Stability

Vogtmann, et al (2017) AJE

12

Accuracy

Vogtmann, et al (2017) AJE

13

Outline

Introduction to the human microbiome Technologies to assess the microbiomeHuman microbiome and colorectal cancer Future directions

14

Colorectal cancer worldwide

15

Meat and colorectal cancer

Cancer Research UK (http://gloriousnutrition.co.uk/processed-meat-popularity-decreasing-due-to-cancer-link/)

16

Meat and the gut microbiome

David et al (2014) Nature

17

Microbiome and colorectal cancer (U.S.)

Ahn et al (2013) JNCI

18

Microbiome and colorectal cancer (U.S.)

Ahn et al (2013) JNCI

Case enrichment

• Fusobacterium

• Veillonellaceae• Anaerovorax

• Porphyromonas

• Atopobium

Control enrichment

• Firmicutes overall• Lachnospiraceae

19

Meta-analysis of 16S rRNA gene studies

Shah et al (2017) Gut

20

Meta-analysis of 16S rRNA gene studies

Shah et al (2017) Gut

21

Potential mechanisms

Drewes et al (2016) BJC

22

Conclusions

There is promise for fecal microbial markers to enhance FOBT or FIT tests for colorectal cancer screening

All previous studies have been cross-sectional

Prospective studies (and studies with multiple serial samples) are needed to understand microbial associations with colorectal cancer etiology

23

Outline

Introduction to the human microbiome Technologies to assess the microbiomeHuman microbiome and colorectal cancer Future directions

24

Future directions

Optimization of collection method for multiple technologies

Collect fecal samples in prospective cohort studies

Quality control standards to evaluate reproducibility

Standardization of methods for extraction, sequencing, and bioinformatics for data pooling and meta-analyses

25

Acknowledgements DCEG Metabolic Epidemiology Branch

Christian Abnet

Gwen Murphy

Rashmi Sinha

DCEG Biostatistics Branch

Jianxin Shi

Xing Hua

Yunhu Wan

DCEG Cancer Genomics Research Laboratory

Belynda Hicks

Amy Hutchinson

Kristie Jones

Casey Dagnall

Shalabh Suman

Bin Zhu

University of Maryland

Owen White

UCSD

Rob Knight

Amnon Amir

University of Guelph

Emma Allen-Vercoe

Mayo Clinic

Nicholas Chia

Jun Chen

Heidi Nelson

Harvard University

Curtis Huttenhower

www.cancer.gov www.cancer.gov/espanol